Smoking Cessation
Conditions
Keywords
crossover
Brief summary
The study will assess a novel active drug vs. placebo on ability to reduce smoking and aid cessation during a one-week practice quit period for each condition in smokers with a high interest in quitting (i.e. crossover design). Medication effects on reducing withdrawal and cognitive impairment will help assess the mechanism to support quit smoking attempts.
Detailed description
We aim to test the proof of principal that an alpha-7 PAM drug, JNJ-39393406, promotes smoking cessation when compared to placebo. We have developed, tested, and validated an efficient Phase 2a screening procedure that optimally combines the validity of randomized clinical trials with the practicality of lab- based medication studies. Notably, it employs a within-subject, cross-over design comparing active versus placebo effects on quitting smoking to maximize statistical power without a large sample, in contrast to the large samples needed for between-groups randomized treatment conditions. Using this procedure, we will evaluate effects of JNJ-39393406 vs. placebo on short-term smoking abstinence in smokers who already have a high interest in quitting soon. We predict that, compared with placebo, JNJ-39393406 will increase days of abstinence, identifying initial evidence of efficacy for smoking cessation. Our main dependent measure is days of very stringent biochemically validated (expired CO\<5 ppm) 24-hr smoking abstinence, with post-quit withdrawal and cognitive function as secondary measures. Potential for adverse side-effects will be assessed at each visit.
Interventions
DRUGActive JNJ Drug
200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.
DRUGPlacebo pill
Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.
Sponsors
National Institutes of Health (NIH)
Chengappa, K.N. Roy, MD
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Crossover of active JNJ vs. placebo for 2 weeks each, involving 1 week of dose run-up and 1 week of attempting to quit each day on that drug condition. A one-week washout separates these drug conditions, which are administered in counter-balanced order.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy male and female dependent smokers wanting to quit soon \-
Exclusion criteria
* Use of non-smoked nicotine products * Already enrolled in cessation program. * Recent alcohol or substance dependence (≤ 3 months) * Women who are pregnant, planning a pregnancy, or lactating; all female participants shall undergo a pregnancy test at screening and will be excluded if positive. * Serious or unstable medical disorder within the past 3 months * Epilepsy * Current diagnosis (within last 6-months) of abnormal cardiac rhythms; unstable cardiovascular disease e.g. stroke, myocardial infarction in the last 6 months * Evidence impaired liver function test (LFT) * Evidence of kidney failure * Any subject with a history of hematological cancers examples: leukemia, lymphoma etc. * Any clinically significant hematological laboratory abnormality.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quit Status | up to one week each drug phase (0-5) | Complete abstinence from smoking for 24 hr is counted as a quit day and is assessed daily from Mon-Fri for just one week, on the JNJ active drug and one week on placebo. This same Mon-Fri procedure for one week (only) is done for both drug phases. Total outcome in each drug condition therefore is number of quit days out of the five assessment days (range 0-5). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo | only on days quit while on JNJ or on placebo | Severity of withdrawal symptoms will be assessed with standard self-report measure of Minnesota Nicotine Withdrawal Scale (MNWS) each quit day during one week only on active JNJ, and each quit day during one week on placebo. Ratings are made on 0-100 visual analog scale, with 0=not at all to 100=very much, and are averaged to create a total score also ranging from 0-100. Higher scores indicate more severe withdrawal. |
| Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods | first day during quit week on JNJ, and during quit week on placebo. | This measure of cognitive performance (mean of median speed of correct responding on computer keyboard to letters and numbers) was assessed only on Monday (day 1) of the 0-5 days during each drug/placebo condition. Data only from those shown to have CO\<10 ppm were analyzed, to confirm responding during abstinence while on drug/placebo condition. Cognitive testing consisted of standard Continuous Performance Task (CPT), on active JNJ and on placebo phases. This measure is assessed to determine potential mechanism of drug efficacy in relieving disrupted cognitive processing function caused by tobacco deprivation and withdrawal. |
Countries
United States
Participant flow
Pre-assignment details
All enrolled after confirmation of eligibility were then assigned to Order 1 or Order 2.
Participants by arm
| Arm | Count |
|---|---|
| Order 1--JNJ Active Then Plac 200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design, then one week trying to quit on placebo. This JNJ experimental compound has NO name, just a company number.
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week. | 18 |
| Order 2--Placebo Then JNJ Active Placebo pill used for one week quit attempt, as part of crossover design, then one week trying to quit on active JNJ drug.
Active JNJ Drug: 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.
Placebo pill: Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week. | 18 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Drug Condition 1: First Study Phase | Withdrawal by Subject | 1 | 3 |
| Drug Condition 2: Second Study Phase | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Order 1--JNJ Active Then Plac | Order 2--Placebo Then JNJ Active | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 18 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 18 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fagerstrom Test of Nicotine Dependence (FTND) scale score | 4.9 units on a scale STANDARD_DEVIATION 1.5 | 4.9 units on a scale STANDARD_DEVIATION 1.5 | 4.9 units on a scale STANDARD_DEVIATION 1.5 |
| Region of Enrollment United States | 18 participants | 18 participants | 36 participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 5 / 36 | 3 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
Quit Status
Complete abstinence from smoking for 24 hr is counted as a quit day and is assessed daily from Mon-Fri for just one week, on the JNJ active drug and one week on placebo. This same Mon-Fri procedure for one week (only) is done for both drug phases. Total outcome in each drug condition therefore is number of quit days out of the five assessment days (range 0-5).
Time frame: up to one week each drug phase (0-5)
Population: Smokers trying to quit each day during 5-day period on active JNJ, and then during 5-day period on placebo, in crossover design.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Order 1--JNJ Active Then Plac | Quit Status | on JNJ | 0.5 number of days quit | Standard Deviation 1.3 |
| Order 1--JNJ Active Then Plac | Quit Status | on placebo | 0.7 number of days quit | Standard Deviation 1.5 |
| Order 2--Placebo Then JNJ Active | Quit Status | on placebo | 0.5 number of days quit | Standard Deviation 1 |
| Order 2--Placebo Then JNJ Active | Quit Status | on JNJ | 0.2 number of days quit | Standard Deviation 0.6 |
Secondary
Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods
This measure of cognitive performance (mean of median speed of correct responding on computer keyboard to letters and numbers) was assessed only on Monday (day 1) of the 0-5 days during each drug/placebo condition. Data only from those shown to have CO\<10 ppm were analyzed, to confirm responding during abstinence while on drug/placebo condition. Cognitive testing consisted of standard Continuous Performance Task (CPT), on active JNJ and on placebo phases. This measure is assessed to determine potential mechanism of drug efficacy in relieving disrupted cognitive processing function caused by tobacco deprivation and withdrawal.
Time frame: first day during quit week on JNJ, and during quit week on placebo.
Population: Only those participants able to quit or sharply limit smoking exposure during both JNJ and the placebo phases of testing, defined as those with CO\<10 during both tests of cognitive performance when tobacco abstinent.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Order 1--JNJ Active Then Plac | Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods | on active JNJ | 444.3 ms time of correct responding | Standard Deviation 69.3 |
| Order 1--JNJ Active Then Plac | Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods | on placebo | 434.2 ms time of correct responding | Standard Deviation 33.5 |
| Order 2--Placebo Then JNJ Active | Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods | on placebo | 439.2 ms time of correct responding | Standard Deviation 28 |
| Order 2--Placebo Then JNJ Active | Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods | on active JNJ | 443.3 ms time of correct responding | Standard Deviation 32 |
Secondary
Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo
Severity of withdrawal symptoms will be assessed with standard self-report measure of Minnesota Nicotine Withdrawal Scale (MNWS) each quit day during one week only on active JNJ, and each quit day during one week on placebo. Ratings are made on 0-100 visual analog scale, with 0=not at all to 100=very much, and are averaged to create a total score also ranging from 0-100. Higher scores indicate more severe withdrawal.
Time frame: only on days quit while on JNJ or on placebo
Population: Withdrawal severity on quit days for smokers interested in quitting soon, while attempting to quit briefly during one week on active JNJ or one week on placebo.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Order 1--JNJ Active Then Plac | Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo | on active JNJ | 12.4 units on a scale | Standard Deviation 8.1 |
| Order 1--JNJ Active Then Plac | Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo | on placebo | 15.5 units on a scale | Standard Deviation 15.2 |
| Order 2--Placebo Then JNJ Active | Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo | on active JNJ | 24.0 units on a scale | Standard Deviation 23.4 |
| Order 2--Placebo Then JNJ Active | Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo | on placebo | 23.1 units on a scale | Standard Deviation 19.8 |